Sexually experienced women are at risk for acquiring sexually transmitted infections (STIs). A potentially important strategy for reducing this risk is the development and use of effective intravaginal microbicides. Because these products will be used by healthy women they will need to have an outstanding safety profile. These products should be neither cytotoxic nor locally immunotoxic and should have no deleterious effects on vaginal flora. In our first specific aim we propose to assess the usefulness of a new imaging technology, optical coherence tomography, to examine for evidence of microbicide-induced injury of the cervical epithelium. Optical coherence tomography (OCT) utilizes light to image the surface of living tissue without disturbing its integrity. We hypothesize that the OCT method will be more sensitive than colposcopy in detecting disruption of the cervical epithelium. In our second specific aim we propose to conduct two Phase I clinical trials of combination products consisting of dendrimers and BufferGel TM. Dendrimers are highly branched, three-dimensional, synthetic macromolecules that can possess antimicrobial activity. BufferGel reduces susceptibility to STIs by maintaining the low pH of the vagina in the presence of semen. Assessment of safety and acceptability will include the effects on pro-inflammatory cytokine responses, vaginal flora, integrity of the cervical epithelium as assessed by colposcopy and optical coherence tomography and acceptability questionnaire. We hypothesize that the combination microbicides will be safe and acceptable.